The experimental approach to the etiology and pathogenesis of the demyelinative disease (MS) will include in vitro and in vivo studies of acute and chronic EAE and acute and chronic M.S. The techniques with which the immunological (T and B-cell) factors and the mechanisms of structural (demyelination, sclerosis), functional (bioelectrical) and chemical alterations will be examined include organotypic cultures of nerve tissues, correlated with intraocular injections into the rabbit, light and electron microscopy, immunochemistry, immunohistochemistry, microelectrode recording of bioelectrical activities and microchemical analyses of enzymes and substrates.